What is the definition of Sepsis‑4.0, including the organ dysfunction criteria and the septic shock parameters?

Sepsis-4.0 Definition

There is no "Sepsis-4.0" definition in current medical literature—the most recent and widely accepted definition remains Sepsis-3, published in 2016 by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. 1

Current Sepsis Definition (Sepsis-3)

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. 1, 2

Organ Dysfunction Criteria

Organ dysfunction is operationalized as an acute increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with in-hospital mortality greater than 10%. 1, 3

SOFA Score Components 3:

• Respiratory System: PaO₂/FiO₂ ratio

  • <400 mmHg = 1 point
  • <300 mmHg = 2 points
  • <200 mmHg with mechanical ventilation = 3 points
  • <100 mmHg with mechanical ventilation = 4 points

• Neurological System: Glasgow Coma Scale

  • 13-14 = 1 point
  • 10-12 = 2 points
  • 6-9 = 3 points
  • <6 = 4 points

• Cardiovascular System: Mean arterial pressure or vasopressor requirement

  • MAP <70 mmHg = 1 point
  • Dopamine ≤5 or dobutamine (any dose) = 2 points
  • Dopamine >5 OR epinephrine ≤0.1 OR norepinephrine ≤0.1 = 3 points
  • Dopamine >15 OR epinephrine >0.1 OR norepinephrine >0.1 = 4 points

• Hepatic System: Bilirubin (mg/dL)

  • 1.2-1.9 = 1 point
  • 2.0-5.9 = 2 points
  • 6.0-11.9 = 3 points

  • 12.0 = 4 points

• Coagulation System: Platelets × 10³/μL

  • <150 = 1 point
  • <100 = 2 points
  • <50 = 3 points
  • <20 = 4 points

• Renal System: Creatinine (mg/dL) or urine output

  • 1.2-1.9 = 1 point
  • 2.0-3.4 = 2 points
  • 3.5-4.9 or <500 mL/day = 3 points

  • 5.0 or <200 mL/day = 4 points

Septic Shock Definition

Septic shock is defined as a subset of sepsis with profound circulatory, cellular, and metabolic abnormalities, clinically identified by: 1, 2, 4

1. Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg 1, 2
2. Serum lactate level >2 mmol/L (>18 mg/dL) 1, 2
3. Both criteria must persist despite adequate volume resuscitation 1, 4

This combination is associated with hospital mortality rates greater than 40%. 1, 4

Key Changes from Previous Definitions

The Sepsis-3 definition eliminated the term "severe sepsis" as redundant and removed the systemic inflammatory response syndrome (SIRS) criteria due to inadequate specificity and sensitivity. 1, 5

Elevated lactate levels (even if >4 mmol/L) are no longer part of organ dysfunction criteria to define sepsis—they are now used only as one of the criteria to define septic shock. 3

Clinical Implications

Mortality rates correlate directly with sepsis severity: no sepsis 1.2%, sepsis only 4.4%, severe sepsis 27.8%, and septic shock 67.8%. 3

Common Pitfalls in Identification 2, 4:

• Failing to recognize perfusion abnormalities in patients receiving vasopressors despite normal blood pressure 2
• Delaying vasopressor initiation while continuing excessive fluid administration 2, 4
• Not measuring lactate levels, which are essential for diagnosis 2
• Confusing septic shock with other forms of distributive shock 2, 6